Remote blood volume monitor

ABSTRACT

Systems and methods are disclosed for providing ongoing monitoring and updating of blood volume status, where the system or method can include guidance in the form of recommendations for treatment actions or alerts about altered patient status.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 16/823,482, filed on Mar. 19, 2020, now allowed, which claimsthe benefit of U.S. Provisional Patent Application No. 62/820,393, filedon Mar. 19, 2019, the contents of both of which are herein incorporatedby reference in their entirety into the present application.

FIELD OF THE INVENTION

The present invention relates to medical diagnosis, monitoring andtreatment of patients. Systems and methods are presented for remotemonitoring of blood volume of a living creature, after an initial bloodvolume measurement has been made.

BACKGROUND OF THE INVENTION

Knowledge of blood volume is important in diagnosing and treatingnumerous medical conditions, including heart failure, hypertension,trauma, sepsis, acute respiratory distress syndrome (ARDS), syncope, andmany others. A blood volume analyzer (BVA) is an instrument or systemcapable of measuring and reporting the volume of blood of a livingbeing. The Daxor BVA-100 Blood Volume Analyzer, based on U.S. Pat. No.5,024,231, is a commercially available, FDA-approved device. It operateson the indicator-dilution principle. I-131-labelled Human Serum Albumin(HSA) is injected into a patient's blood stream, and various samples ofblood are taken at timed intervals after mixing has occurred. Othertracers have been employed to measure blood volume, including dyes suchas Evans Blue, fluorescent compounds such as ICG, and other radioactivetracers such I-125 and Cr-51. These compounds have been used to labelnaturally occurring blood components (typically plasma proteins such asalbumin or entire red blood cells), other molecules of various sizeswhich can safely be introduced into the bloodstream, or as a nakedtracer. Regardless of the tracer and exact method used, theindicator-dilution technique presents challenges for both repeatedmeasurements of blood volume status, and for ongoing monitoring of bloodvolume status. Some tracers (especially radioactive ones) may havecumulative exposure limits for patients that may make multiplemeasurements undesirable or impossible. Tracer clearance from thebloodstream is an important issue: a tracer that clears too slowly fromthe bloodstream will interfere with the accuracy of subsequent tests(even if background measurements are taken); a tracer that clears tooquickly from the bloodstream may not provide accurate measurements ofblood volume in the first place. Beyond issues related to the use of atracer, there are also practical issues related to the performance ofthe method, namely that it is a relatively complex test that isperformed in a hospital or clinical setting, by a technician who hasreceived specialized training, and requires a specialized compound to beadministered to the patient through an IV, and at least one sample ofblood to be taken at a measured time interval. It would be beneficial tobe able to monitor blood volume status much more conveniently. Thisimproved convenience could be manifested as one or more of thefollowing: capability for frequent or continuous monitoring of bloodvolume status; ability for follow-up testing to be performed by nurse orother medical professional with no specialized training, or by anindividual (such as the patient) with no medical training. Such a moreconvenient follow-up test would almost certainly cost less to provide.

So-called “Relative Blood Volume Monitoring” using changes in Hct hasbeen disclosed (for example by the Blood Volume Monitor for use duringdialysis, as marketed by Fresenius) but such monitors have notincorporated the measurement of actual (i.e., absolute) blood volume.Without the knowledge of actual blood volume, any observed changes inHct cannot be related to normal values for blood volume for a givenpatient, or indeed even to actual volumes of fluid (since the Hct onlyprovides information about the relative proportions of fluid in thebloodstream).

The knowledge derived from frequent or continuous monitoring of bloodvolume status can be used to guide treatment for a patient, just asknowledge from an initial blood measurement can be used to guidetreatment. Such guidance is the subject of U.S. patent application Ser.No. 16/667,945, “BLOOD VOLUME ANALYZER WITH GUIDANCE”, filed Oct. 30,2019 (U.S. Patent Application Publication No. 2020/0132676 A1, publishedApr. 30, 2020). The disclosures of this publication are herebyincorporated by reference in their entirety into the subject applicationto more fully describe the art to which the subject invention pertains.

The knowledge derived from a blood volume measurement can shed light onother blood tests, for example by euvolemic correction of measuredconcentrations, as is discussed in U.S. Pat. No. 11,204,356 B2, “BLOODVOLUME ANALYSIS WITH VOLUME-AWARE BLOOD COMPONENT MEASURES ANDTREATMENT”, filed Jan. 29, 2018. The disclosures of this publication arehereby incorporated by reference in their entirety into the subjectapplication to more fully describe the art to which the subjectinvention pertains.

SUMMARY OF THE INVENTION

The present invention discloses systems and methods for providingongoing updating and monitoring of blood volume status. In someembodiments, the system or method also includes guidance, e.g. in theform of recommendations for treatment actions or alerts about alteredpatient status.

In one preferred embodiment, a system or method includes a blood volumeanalyzer capable of performing an initial blood volume evaluation, andof storing the results. Also included is a component for enteringinformation about how the patient's red cell status is changing. Alsoincluded is a component for measuring patient Hct at subsequent times,and of communicating such measurements to the analyzer, which updatesits results (including current patient values, as well as deviationsfrom patient ideal values) in the form of an updated or continuouslyupdated report.

In one preferred embodiment, the information about the patient's redcell status is entered manually by a user, and quantifies the volume ofred cells that may have been added by transfusion, and/or that may havebeen lost to bleeding, or specifies that red cell volume has beenstable.

In one preferred embodiment, the information about red cell additions istransmitted to the analyzer automatically by a component that bothperforms the transfusion of a known volume of red cells and communicateswith the analyzer.

In one preferred embodiment, the information about blood loss istransmitted to the analyzer automatically by a component that bothmeasures the loss of blood due to bleeding, and communicates with theanalyzer. In another preferred embodiment, the Hct measurement is usedto update the patient's red cell status, under the assumption that totalblood volume is stable, and alerts are given when the patient passesthresholds of red cell volume defining anemia.

In one preferred embodiment, the component for measuring Hct is a remotemonitor which communicates its reading of Hct to the analyzer (baseunit), such that updated measurements, guidance and alerts are madeavailable to medical personnel via the base unit, and/or to the patientvia the remote monitor.

In various preferred embodiments, customized, patient-specific guidanceis produced based on published protocols, and the values calculated inan updated blood volume measurement. Such guidance is used to treatspecific conditions such as Heart Failure, Hypertension, etc.

In various other preferred embodiments, the component for measuring Hctis combined with one or more other monitoring devices for other medicalinformation; the combination of monitors allows the other devices' datato be adjusted by knowledge of volume status, and to be taken intoaccount in the guidance provided by the system.

In one preferred embodiment for Heart Failure, the monitoring device isa Photo-plethysmography (PPG) sensor embedded in a wristband or otherwearable garment or device, which in addition to monitoring Hct also isconfigured to detect and send alerts regarding changes in resting heartrate, changes in resting respiration rate, and episodes of atrialfibrillation (Afib).

In one embodiment for Heart Failure, an estimate of blood volume statusis used in place of an initial blood volume measurement, where theestimate is derived from a combination of clinical judgment based onobservation and available tests along with historical reference data forblood volume in similar patients, which indicate that volume overload iscommon in these patients. Similarly, in an embodiment for Syncope, anestimate of blood volume status is used in place of an initial bloodvolume measurement, where the estimate is derived from a combination ofclinical judgment based on observation and available tests along withhistorical reference data for blood volume in similar patients, whichindicate the volume deficit is common in these patients. In a preferredembodiment for Syncope, the monitoring device is a PPG sensor embeddedin a wristband or other wearable garment or device, which in addition tomonitoring Hct also is configured to detect and send alerts regardingdifferences between heart rate when sitting and standing, changes inresting heart rate, changes in resting respiration rate, and episodes ofatrial fibrillation (Afib). In an embodiment for monitoring anemia, anestimate of blood volume status with red cell deficit is used in placeof an initial blood volume measurement. In a preferred embodiment foranemia, the monitoring device is a PPG sensor embedded in a wristband orother wearable garment or device, which in addition to monitoring Hctalso is configured to detect and send alerts regarding tachycardia,changes in resting heart rate, changes in resting respiration rate, andepisodes of atrial fibrillation (Afib). In an embodiment for monitoringpolycythemia, an estimate of blood volume status with red cell excess isused in place of an initial blood volume measurement. In anotherembodiment, positive alerts are triggered when blood volume thresholdsare passed indicating that the patient's condition has improved ratherthan worsened.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a preferred embodiment of the system. A blood volumeanalyzer with guidance performs a volume measurement of patient XYZ. Theanalyzer produces an initial report of the patient's volume status,including guidance. A Hct monitor provides regular (or continuous)measurements of Hct, which are delivered to the analyzer. As Hctinformation and/or manual red cell information changes, an updatedreport is produced.

FIG. 2 shows a preferred embodiment of the system, in which remotemonitoring is used to guide treatment for patients after an initialBlood Volume measurement.

FIG. 3 shows details of various embodiments of the Hct Monitor andTransceiver, variously as an integrated device, or as comprised ofvarious discrete elements.

FIG. 4 shows various embodiments of a system which incorporatesadditional monitors which can supplement the Hct reading with additionalpatient data readings.

FIG. 5 shows an embodiment of a generic system in which a concentrationcounter measures the concentration of a tracer in a patient's blood atan initial time, and a Hct monitor measures patient Hct at an initialand subsequent time; these measurements are used to calculate andpresent an initial and updated report of patient blood volume status.

DETAILED DESCRIPTION OF THE INVENTION

It is assumed that a Blood Volume Analysis is available for a patient,including values for the following quantities: Blood Volume (BV), PlasmaVolume (PV), Red Cell Volume (RCV), and that normal values are alsoderived from knowledge of the patient's gender, height and weight: IdealBlood Volume (iBV), Ideal Plasma Volume(iPV) and Ideal Red CellVolume(iRCV). Such values can be derived by consulting the relationshipdescribed in “Prediction of the Normal Blood Volume” (Feldschuh et al,Circulation, vol. 56, No. 4, Oct. 1977, pp. 605-612.). In a preferredembodiment, all these values are taken from an automated Blood VolumeAnalyzer such as described in U.S. Pat. No. 5,024,231. This analyzeruses radio-labeled I-131. The contents of that patent are hereinincorporated by reference. It is also assumed that a peripheralhematocrit (pHct) is available. In a preferred embodiment, these valuesare taken from a “Blood Volume Analysis with Volume-Aware BloodComponent Measures and Treatment” such as described in U.S. Pat. No.11,204,356 B2. In another preferred embodiment, these values are takenfrom a “Blood Volume Analyzer with Guidance” such as described in U.S.patent application Ser. No. 16/667,945 (U.S. Patent ApplicationPublication No. 2020/0132676 A1, published Apr. 30, 2020).

The overall whole body Hct (oHct) is related to the peripheral Hct bythe following relationship:

oHct=pHct*paf  (1)

where

paf=0.9009  (2).

This is due to the fact that blood cells are more concentrated in theperipheral circulation (from which blood samples are drawn) than theaverage value for the whole body; the constant paf is derived as theproduct 0.99*0.91, as described in U.S. Pat. No. 5,024,231, or a similarconstant value. Red Cell Volume and Plasma volume are related to BloodVolume as follows:

BV=PV+RCV  (3)

RCV=BV*oHct=BV*pHct*paf  (4)

PV=BV*(1−oHct)=BV*(1−pHct*paf)  (5).

The Ideal Hct (iHct) is defined to be:

$\begin{matrix}{{iHct} \equiv \left\{ {\begin{matrix}{0.45{for}{Males}} \\{0.4{for}{Females}}\end{matrix}.} \right.} & (6)\end{matrix}$

The Ideal Red Cell Volume (iRCV) and Ideal Plasma Volume (iPV) arecalculated from the iBV. Note that the iHct is a peripheral Hct value,so the peripheral adjustment factor is required:

iBV=iPV+iRCV  (7)

iRCV=iBV*iHct*paf  (8)

iPV=iBV−iRCV=iBV*(1−iHct*paf)  (9).

Guidance for treatment may be determined with reference to absolutedeviations from ideal volumes, where the abbreviation “dev” is definedto be the deviation of a measured value from its respective Ideal value:

devBV=BV−iBV  (10)

devRCV=RCV−iRCV  (11)

devPV=PV−iPV  (12).

Guidance for treatment may also be determined with reference topercentage deviations from ideal volumes, where the abbreviation “edr”is defined to be the excess-deficit ratio of the deviation of a measuredvalue from its respective Ideal value:

$\begin{matrix}{{edrBV} = \frac{devBV}{iBV}} & (13)\end{matrix}$ $\begin{matrix}{{edrRCV} = \frac{devRCV}{iRCV}} & (14)\end{matrix}$ $\begin{matrix}{{edrPV} = {\frac{devPV}{iPV}.}} & (15)\end{matrix}$

This allows volume-aware metrics to be defined that incorporate actualand ideal volume measurements into a single ratio-like (i.e. unit-less)value.

After an initial measurement of Blood Volume status has been performed,it may be desirable to have an updated measurement, but without theinconvenience, effort, technical difficulties, etc. of performingsubsequent direct measurements of BV using the indicator dilutionmethod. The subscript “u” is used to indicate updated values, and “f” toindicate first (initial) values. The first measurement was performed attime t_(f), and an updated measurement at time t_(u). An updatedperipheral Hct pHct_(u) is obtained (e.g. using a subsequent blood drawand spun Hct, or via an inline monitor or other means). Consider a casein which we know that the RCV is unchanged. This will be the case, forexample, if all of the following are true:

-   -   1) a relatively short time has elapsed since the first        measurement (i.e. t_(u)-t_(f) is relatively small), such that        only negligible net production or destruction of red cells via        internal processes is likely to have occurred    -   2) no bleeding has occurred    -   3) no blood products have been administered.

For this case RCV_(u)=RCV_(f). Because of assumption 1) above, one canalso assume that ideal volume values have remained constant, as theseare calculated solely from patient gender, height, and weight. Thisimplies that iBV_(u)=iBV_(f), iPV_(u)=iPV_(f), and iRCV_(u)=iRCV_(f).Updated values are calculated as follows. Rewriting equations 4 and 5 toexpress BV and PV in terms of RCV:

$\begin{matrix}{{BV} = \frac{RCV}{pHct*paf}} & (16)\end{matrix}$ $\begin{matrix}{{PV} = {{RC}V*\frac{\left( {1 - {pHct*paf}} \right)}{pHct*paf}}} & (17)\end{matrix}$

Now using the assumption

RCV _(u) =RCV _(f)  (18)

updated formulas for BV and PV are derived that depend only on anupdated value for pHct.

$\begin{matrix}{{BV_{u}} = \frac{RCV_{f}}{pHct_{u}*paf}} & (19)\end{matrix}$ $\begin{matrix}{{PV}_{u} = {RCV_{f}*\frac{\left( {1 - {pHct_{u}*paf}} \right)}{pHct_{u}*paf}}} & (20)\end{matrix}$

Using the updated values, and noting that updated values for the idealvalues are not required (as discussed above), one can also obtainupdated deviations to use in generating guidance:

devBV_(u) =BV _(u) −iBV  (21)

devRCV_(u) =RCV _(u)−iRCV=devRCV_(f)  (22)

devPV_(u) =PV _(u) −iPV  (23)

And similarly:

$\begin{matrix}{{{edrB}V_{u}} = \frac{devBV_{u}}{iBV}} & (24)\end{matrix}$ $\begin{matrix}{{{edrRC}V_{u}} = {\frac{devRCV_{u}}{iRCV} = {edrRCV_{f}}}} & (25)\end{matrix}$ $\begin{matrix}{{{edrP}V_{u}} = {\frac{devPV_{u}}{iPV}.}} & (26)\end{matrix}$

Now consider the case where the assumption that RCV is unchanged is notmade. In this case the updated RCV is described in terms of theprocesses discussed in the three numbered assumptions above. DefineR_(internal) as the net change in red cell volume due to ongoinginternal processes of red cell production and destruction, R_(added) asthe volume of red cells added via blood products, and R_(lost) as thevolume of red cell lost to bleeding.

ΔRCV≡RCV _(u) −RCV _(i)

ΔRCV=R _(internal) +R _(added) −R _(lost)  (27)

To the extent that ΔRCV can be quantified, one can generalize equations(18)-(20) to derive updated volume figures in terms of pHct_(u) and ΔRCVas follows:

RCV _(u) =RCV _(f) +ΔRCV  (28)

$\begin{matrix}{{BV_{u}} = \frac{{RCV_{f}} + {\Delta RCV}}{pHct_{u}*paf}} & (29)\end{matrix}$ $\begin{matrix}{{PV}_{u} = {\left( {{RCV}_{f} + {\Delta{RCV}}} \right)*\frac{\left( {1 - {pHct_{u}*paf}} \right)}{pHct_{u}*paf}}} & (30)\end{matrix}$

The equations for deviations (21)-(26) can now be used with thesegeneralized values.To what extent can the components of ΔRCV can be quantified withconfidence? The applicability of an updated BVA measurement using ΔRCVdepends on that confidence.

The R a dd e d component will generally be well knowable, as bloodproducts are usually administered in discrete units. Then the addedvolume is simply the product of the number of units N_(units) and theRCV_(unit) of a single unit:

R _(added) =N _(units) *RCV _(unit)  (31)

For example, in the U.S., blood units are prepared from 500 ml of donorblood. The RCV_(unit) would be 200 ml if the donor blood had a pHct of40%, but this number could vary based on the possible acceptance rangefor donor blood, which is not the same everywhere, and varies for maleand female donors. A fixed value such as 200 ml could be assumed forRCV_(unit). A more precise value for a given patient could also begenerated by measuring the actual volume of the units administered,either directly as they are infused, or indirectly by weighing theunits, subtracting the weight of the packaging, and using an assumedvalue for the volume of red cells to the weight of packed cells. Such aratio can be estimated from the typical 70% Hct_(blood) of packed redcells, and the specific gravity of blood of 1.06 g/cm³:

$\begin{matrix}{{RCV}_{unit} = {\left( {{Weight}_{unit} - {Weight}_{pac{kaging}}} \right)*{\frac{{Hct}_{blood}}{{specific}{gravity}_{blood}}.}}} & (32)\end{matrix}$

Estimating R_(lost) is sometimes done in the course of surgery, whenblood loss is quantified via recaptured blood and/or weighing ofabsorbent materials. The accuracy of such measures, and of otherclinical estimates of blood loss is a matter of clinical discretion. Forstable patients who have not undergone surgery, it may be reasonable toassume R_(lost)=0.

Estimating R_(internal) is most useful for short to moderate timeintervals. Red blood cell production (erythropoiesis) takes place in thebone marrow and is moderated by the hormone erythropoietin (EPO), and isaffected by numerous factors, particularly the availability ofsufficient iron. Red blood cell lifetime is estimated to be 120 days, soan ongoing replacement level of both production and destruction could beassumed to be 1/120 of iRCV. Estimating the net internal change for aparticular patient is a matter of clinical discretion, with uncertaintyincreasing approximately linearly with time. For follow-up periodssignificantly less than 120 days, it may be reasonable to assumeR_(internal)=0.

The invention provides a system for automatically analyzing blood of aliving patient, comprising a concentration counter configured to analyzethe patient's blood, a user interface operatively connected to theconcentration counter and configured for entry and display ofinformation, a Hematocrit(Hct) monitor, and one or more processorsoperatively coupled to a memory and configured to execute programmedinstructions stored in the memory to carry out a method comprising thesteps of: a) gathering data from the concentration counter, related tothe concentration of a tracer within the of blood of a patient, and fromthe Hct monitor; b) calculating, by the one or more processors, a bloodvolume (BV), plasma volume (PV), and red cell volume (RCV) for thepatient; c) calculating, by the one or more processors, an ideal bloodvolume (iBV), ideal plasma volume (iPV), and red cell volume (iRCV) forthe patient based on patient descriptive data such as height, weight,and gender; d) displaying, by the one or more processors, at the userinterface, the results of steps (b) and (c); e) storing for later usethe results of steps (b) and (c); f) measuring, at one or more latertimes, an updated value for patient Hematocrit (Hct); g) calculating, bythe one or more processors, updated values for BV, PV, and RCV based onthe updated Hct, without performing additional measurements related tothe concentration of a tracer within the blood of the patient; and h)displaying, by the one or more processors, at the user interface, theresults of step (g).

The Hct Monitor should be understood as any device or component capableof performing at least one measurement of Hct on the blood a livingsubject, either directly applied to the subject or to blood sampled fromthe subject. The mechanism of this measurement may take any form thatresults in an acceptably accurate measurement. Examples of suchmechanisms include direct observation of the proportion of plasma andred cells in a spun sample of blood (such as in a microcentrifuge);measurement of concentrations of substances in the sample such asHemoglobin that can be correlated and translated to a Hct measurement;measurement of blood flow directly in the living subject via PPG orother optical means, that can be correlated and translated to a Hctmeasurement.

The invention also provides such a system where step a) described hereinabove involves the injection of a tracer into the patient prior tomeasuring (either in vivo or using collected in vitro samples) theconcentration of the samples. The tracer used can be a radioactiveisotope (for example I-131), or a light-emitting substance (such asfluorescent ICG or fluorescein) or light-absorbing (such as Evans bluedye).

The invention provides for the performance of step (g) described hereinabove using the assumption that RCV is unchanged, and updated BV_(u) andPV_(u) values are calculated from the first RCV f value and the updatedperipheral Hct value (pHct_(u)) and peripheral adjustment factor (paf),where paf takes on a constant value such as 0.9009: RCV_(u)=RCV_(f),

${{BV_{u}} = \frac{RCV_{f}}{pHct_{u}*paf}},{{PV}_{u} = {Rcv_{f}*{\frac{\left( {1 - {pHct_{u}*paf}} \right)}{pHct_{u}*paf}.}}}$

The invention provides for the performance of step (g) described hereinabove using a value for the change in RCV (ΔRCV), and updated BV_(u)RCV_(u), and PV_(u) values are calculated from the first RCV_(f) value,pHct_(u) and paf: RCV_(u)=RCV_(f)+ΔRCV,

${{Bv_{u}} = \frac{{RCV_{f}} + {\Delta RCV}}{pHct_{u}*paf}},{{PV}_{u} = {\left( {{RCV_{f}} + {\Delta Rcv}} \right)*{\frac{\left( {1 - {pHct_{u}*paf}} \right)}{pHct_{u}*paf}.}}}$

The invention provides for the performance of step (g) described hereinabove where ΔRCV is estimated according to the formulaΔRCV=R_(internal)+R_(added)−R_(lost).

The invention provides for the performance of step (g) described hereinabove where R_(added) is estimated based on the number and size of unitsof blood products administered.

The invention provides for the performance of step (g) described hereinabove where R_(lost) is estimated based on a measurement of blood lossduring a medical procedure.

The invention provides for the system described herein where in additiontreatment guidance is calculated based on the patient values, usingprotocol-derived rules stored within the system, and containingquantified patient-specific treatment information; and such guidance isdisplayed at the user interface by the one or more processors, based onthe original BV calculation: after step (d), and based on the updated BVcalculation after step (h). The treatment guidance may be presented intextual form, or in flow-chart form. The protocols for the system may bederived from one or more published protocols relating to blood volumemanagement. Such protocols may be customizable by the user, to includeone or more of the following features: alteration of thresholds forconsideration of a treatment; addition of a treatment option; removal ofa treatment option; alteration of the calculation for the quantity of atreatment, or alteration of the order of treatment options. The systemmay include one or more treatment capabilities that are connected to thesystem, such that quantified treatment can be administered to a patientby the system; such treatment may be automatic, or may require humanapproval at the time of, or before, administration. Such treatments mayinclude: addition of saline or saline-equivalent fluids; addition ofplasma or other oncotic-support fluids; addition of blood products suchas packed red cells, whole blood, platelets, etc.; removal of fluids viadialysis or ultrafiltration; removal of red cells viaerythrocytapheresis; manipulation of a drug (stopping/starting/adjustingdosage) that is connected to a patient via IV or oral means. Theprotocols may be customized to include other patient information besidesBV, PV, RCV, iBV, iPV, and iRCV; such information may be entered by theuser manually into the system or accessed via a network connection tothe patient's medical records. The protocols may be customized to dealwith specific patient conditions beyond the scope of simple volumemanagement, but where knowledge of volume influences treatmentdecisions. Such conditions include Heart Failure, Syncope, Critical Care(including Sepsis and ARDS), Hypertension, and Renal Failure/Dialysis.An example of a heart failure protocol that deals with blood volume isthe “2013 ACCF/AHA Guideline for the Management of Heart Failure” whichstates that “Volume status and vital signs should be assessed at eachpatient encounter.” An example of a syncope protocol that deals withblood volume is the “2018 ESC Guidelines for the diagnosis andmanagement of syncope” which contains extensive discussion of volumedepletion as a possible cause of syncope. An example of a critical careprotocol that deals with blood volume is the “The European guideline onmanagement of major bleeding and coagulopathy following trauma: fourthedition” which contains extensive discussion of blood volumerestoration, and includes percentage of blood volume loss indistinguishing the severity of hypovolemic shock (Class I-IV, as per theAmerican College of Surgeons Advanced Trauma Life Support (ATLS)classification); each class is associated with differing treatmentrecommendations. An example of a hypertension protocol that deals withblood volume is the “2017 Guideline for the Prevention, Detection,Evaluation, and Management of High Blood Pressure in Adults: A report ofthe American College of Cardiology/American Heart Association Task Forceon Clinical Practice Guidelines” which contains differential treatmentrecommendations based on the presence of volume depletion or volumeoverload. An example of a renal failure/dialysis protocol that dealswith blood volume is the journal article “Blood volume analysis as aguide for dry weight determination in chronic hemodialysis patients: acrossover study” (Malha et al. BMC Nephrology 2019) which containsextensive discussion of the use of blood volume to obtain betteroutcomes.

The invention provides for the system described herein where the Hctmonitor is located at a separate (remote) location to the concentrationcounter that performs step (a), and which connects with the rest of thesystem via data communications. The remote Hct monitor may take the formof: an integrated monitor and transceiver component; one Hct componentwhich is connected to separate computing device (such as a computer,smartphone, smartwatch, tablet, etc.); one Hct component, where datacommunications with the rest of the system are handled by manual means(such as telephone, email, fax, etc.). The Hct monitor may be equippedwith one or more processors, so as to receive or calculate updatedresults and guidance, and a display interface, to display results andguidance to a remote user. The Hct Monitor may be connected to one ormore additional monitors, and the information from said monitors isconsidered in the calculation of guidance. Such additional monitorsinclude: a Blood Pressure Monitor; a Glucose Monitor, whose measuredWhole blood glucose may or may not be euvolemically corrected toEuvolemic plasma glucose; a Pulse Monitor; a Photo-plethysmography (PPG)Monitor; an Electro-Magnetic (EM) Monitor; a Blood Gas Monitor; aComprehensive Blood Monitor. A monitor that has the capability ofmeasuring Hct itself (such as a Comprehensive Blood Monitor or a PPGmonitor) may be integrated as a Monitor and Transceiver offeringadditional guidance as well.

The invention provides for a method of analyzing the blood of a livingpatient, comprising: a) analyzing the blood of the patient with thesystem described herein to obtain a first patient blood volumemeasurement; and b) at one or more later times, measuring the patientHct and using that value to calculate updated blood volume measurementswithout repeated concentration measurements. Step b) may be performedusing the assumption that RCV is unchanged, and updated BV_(u) andPV_(u) values are calculated from the first RCV f value and the updatedperipheral Hct value (pHct_(u)) and peripheral adjustment factor (paf),where paf takes on a constant value such as 0.9009:RCV_(u)=RCV_(f),

${{BV}_{u} = \frac{RCV_{f}}{pHct_{u}*paf}},{{PV}_{u} = {RcV_{f}*{\frac{\left( {1 - {pHct_{u}*paf}} \right)}{pHct_{u}*paf}.}}}$

Step b) may also be performed using a value for the change in RCV(ΔRCV), and updated BV_(u) RCV_(u), and PV_(u) values are calculatedfrom the first RCV_(f) value, pHct_(u) and paf: RCV_(u)=RCV_(f)+ΔRCV,

${{BV_{u}} = \frac{{RCV}_{f} + {\Delta{RCV}}}{pHct_{u}*paf}},{{PV}_{u} = {\left( {{RCV}_{f} + {\Delta{RCV}}} \right)*{\frac{\left( {1 - {pHct_{u}*paf}} \right)}{pHct_{u}*paf}.}}}$

The value for ΔRCV may be estimated according to the formulaΔRCV=R_(internal)+R_(added)−R_(lost). The value for R_(lost) may beestimated based on the number and size of units of blood productsadministered. The value for R_(added) may be estimated based on ameasurement of blood loss during a medical procedure.

The invention also provides for a method of analyzing the blood of aliving patient, comprising: a) analyzing the blood of the patient withthe system described herein to obtain a first patient blood volumemeasurement; and b) at one or more later times, measuring the patientHct and using that value to calculate updated blood volume measurementswithout repeated concentration measurements, and provide treatmentguidance.

The invention also provides for a method of analyzing the blood of aliving patient, comprising: a) analyzing the blood of the patient withthe system described herein that includes a remote monitor, to obtain afirst patient blood volume measurement; and b) at one or more latertimes, measuring the patient Hct and using that value to calculateupdated blood volume measurements without repeated concentrationmeasurements.

The invention provides a system for automatically analyzing blood of aliving patient, comprising a Hct monitor, a user interface operativelyconnected to the concentration counter and configured for entry anddisplay of information, and one or more processors operatively coupledto a memory and configured to execute programmed instructions stored inthe memory to carry out a method comprising the steps of: a) gatheringor receiving data from the user interface, regarding a specified initialdeviation from ideal blood volume status, and patient descriptive data,and from the Hct monitor; b) calculating, by the one or more processors,an ideal blood volume (iBV), ideal plasma volume (iPV), and red cellvolume (iRCV) for the patient based on patient descriptive data such asheight, weight, and gender; c) calculating, by the one or moreprocessors, a blood volume (BV), plasma volume (PV), and red cell volume(RCV) for the patient based on data gathered or received in step (a); d)displaying, by the one or more processors, at the user interface, theresults of steps (b) and (c); e) storing for later use the results ofsteps (b) and (c); f) measuring, at one or more later times, an updatedvalue for patient Hematocrit (Hct); g) calculating, by the one or moreprocessors, updated values for BV, PV, and RCV based on the updated Hct,without performing additional measurements related to the concentrationof a tracer within the blood of the patient; and h) displaying, by theone or more processors, at the user interface, the results of step (g).

The invention also provides for a Heart Failure Decompensation Monitor,using the system of

In heart failure, it is generally assumed that patients have volumeoverload, especially when external signs of overload in the vascularspace (such as edema, jugular venous distention, etc.) are present.Heart failure patients are also often subject to complications fromanemia (i.e., low red cell blood volume). While it would be best to usean absolute blood volume measurement to anchor relative blood volumecalculations as described herein above, it is also possible to use adefault value for an initial blood volume state for the patient, basedon an estimate using clinical judgment based on observation andavailable tests, combined with historical reference data for bloodvolume in similar patients, which indicate that volume overload withanemia is common in these patients. Once this default reference isestablished, then a monitoring solution specific to heart failure couldincorporate alerts to the patient and/or the clinician. Updated valuesfor TBV, RCV, and PV are calculated in step (g) as described hereinabove in [0035] through [0039]. Alerts are triggered when Hct-derivedvolume values (based on patient default or actual absolute volumestatus) reach a set threshold for TBV above the initial TBV value. Forexample, a patient with an assumed initial TBV of +15% with a Hct of 38has his Hct drop towards 30. This results in a recalculated TBV of +21%at Hct=36, +28% at Hct=34, +36% at Hct=32, and +45% when Hct=30. Thiscan be used to trigger alerts (of escalating severity) based ondifferent levels of recalculated TBV variation. Alerts could also beprovided for other aspects of heart function as detected by PPG (asothers have used in smartwatch-based alert systems, but withoutconnection to volume measures), such as changes in resting heart rate,changes in resting respiration rate, and episodes of atrial fibrillation(Afib). The invention provides for treatment guidance in response toalerts. Treatment for heart failure decompensation includes one or moreof the following: summoning a patient for a consultation with aclinician, to the emergency room, or to receive additional testing suchas blood tests, an X-ray, or stress test; prescribing the patient towear an additional continuous monitor such as an EKG; prescribing orincreasing the dose of a diuretic to relieve volume overload;prescribing or increasing the dose of nitrates; prescribing orincreasing the dose of inotropes; prescribing or increasing the dose ofvasopressors; or prescribing the use of continuous positive airwaypressure (CPAP) mask ventilation. The invention also provides for amethod of treating heart failure patients using this system, consistingof determining one or more TBV threshold values, monitoring the patientwith the system described herein, and prescribing treatment in responseto alerts received.

The invention also provides for a Syncope Monitor, using the system of[0045]. One major cause of syncope is insufficient blood volume. Whileit would be best to use an absolute blood volume measurement to anchorrelative blood volume calculations as described herein above, it is alsopossible to use a default value for an initial blood volume state forthe patient, based on an estimate using clinical judgment based onobservation and available tests, combined with historical reference datafor blood volume in similar patients, which indicate that an initialvolume deficit (e.g. −10% TBV from ideal value) might be used. Althoughnot all cases of syncope are caused by hypovolemia, decreasing bloodvolume in a patient with this condition would be noteworthy. Once thisdefault reference is established, then a monitoring solution specific tosyncope could incorporate alerts to the patient and/or the clinician.Updated values for TBV are calculated in step (g) as described hereinabove in through

with the most likely scenario being no change in red cell volume. Alertsare triggered when Hct-derived volume values (based on patient defaultor actual absolute volume status) reach a set threshold for TBV belowthe initial TBV value. For example, a patient with an assumed initialTBV of −10% with a Hct of 40 has her Hct drop towards 30. This resultsin a recalculated TBV of −14% at Hct=42, −18% at Hct=44, and −20% whenHct=45. This can be used to trigger alerts (of escalating severity)based on different levels of recalculated TBV variation. Alerts couldalso be provided for other aspects of heart function as detected by PPG,such as changes in resting heart rate, changes in resting respirationrate, and episodes of atrial fibrillation (Afib), and thesyncope-specific signal of differences between heart rate when sittingand standing. The invention provides for treatment guidance in responseto alerts. Treatment for lowered volume in syncope includes one or moreof the following: summoning a patient for a consultation with aclinician, to the emergency room, or to receive additional testing suchas an electrocardiogram, echocardiogram, stress test, blood tests,autonomic reflex testing, a tilt table test, neurological testing, or aCT scan; prescribing the patient to wear an additional continuousmonitor; prescribing or increasing the dose of fludrocortisone acetate;recommending an increase in salt intake; and recommending the use ofsupportive garments, strengthening exercises, or other behavioralmodifications. The invention also provides for a method of treatingsyncope patients using this system, consisting of determining one ormore TBV threshold values, monitoring the patient with the systemdescribed herein, and prescribing treatment in response to alertsreceived.

The invention also provides for an Anemia Monitor, using the system of[0045]. In some patients with anemia without other complications such asheart failure, it can be assumed that TBV is stable. While it would bebest to use an absolute blood volume measurement to anchor relativeblood volume calculations as described herein above, it is also possibleto use a default value for an initial blood volume state for thepatient, based on an estimate using clinical judgment based onobservation and available tests, combined with historical reference datafor blood volume in similar patients, which indicate that an initial redcell volume deficit (e.g. −15% RCV from ideal value) might be used. Oncethis default reference is established, then a monitoring solutionspecific to anemia could incorporate alerts to the patient and/or theclinician. Updated values for TBV, RCV, and PV are calculated using thefollowing simple equations: BV_(u)=BV_(f) andRCV_(u)=BV_(f)*pHct_(u)*paf. Alerts are triggered when Hct-derivedvolume values (based on patient default or actual absolute volumestatus) reach a set threshold for RCV below the initial RCV value. Forexample, a patient with an assumed initial RCV of −15% with a startingHct of 36 would have a recalculated RCV of −20% at Hct=34, −24% atHct=32, and −29% when Hct=30. This can be used to trigger alerts (ofescalating severity) based on different levels of recalculated RCVvariation. Alerts could also be provided for other aspects of heartfunction as detected by PPG, such as tachycardia, changes in restingheart rate, changes in resting respiration rate, and episodes of Afib.The invention provides for treatment guidance in response to alerts.Treatment for anemia includes one or more of the following: summoning apatient for a consultation with a clinician, to the emergency room, orto receive additional testing such as blood tests (hemoglobin (Hg), meancellular volume (MCV), ferritin, serum iron (FE), transferrin, totaliron-binding capacity (TIBC), or iron saturation), urine tests, stooltests, ultrasound, or a stress test; prescribing the patient to wear anadditional continuous monitor; recommendations for increased dietaryiron intake; prescriptions for medicinal iron, IV iron, or bloodtransfusions. The invention also provides for a method of treatinganemia patients using this system, consisting of determining one or moreRCV threshold values, monitoring the patient with the system describedherein, and prescribing treatment in response to alerts received.

The invention also provides for a Polycythemia Monitor, using the systemof [0045]. In some patients with polycythemia without othercomplications such as heart failure, it can be assumed that TBV isstable. While it would be best to use an absolute blood volumemeasurement to anchor relative blood volume calculations as describedherein above, it is also possible to use a default value for an initialblood volume state for the patient, based on an estimate using clinicaljudgment based on observation and available tests, combined withhistorical reference data for blood volume in similar patients, whichindicate that an initial red cell volume excess (e.g. +15% RCV fromideal value) might be used. Once this default reference is established,then a monitoring solution specific to polycythemia could incorporatealerts to the patient and/or the clinician. Updated values for TBV, RCV,and PV are calculated using the following simple equations:BV_(u)=BV_(f) and RCV_(u)=BV_(f)*pHct_(u)*paf. Alerts are triggered whenHct-derived volume values (based on patient default or actual absolutevolume status) reach a set threshold for RCV above the initial RCVvalue. For example, a patient with an assumed initial RCV of +15% with astarting Hct of 49 would have a recalculated RCV of +20% at Hct=52,+26.7% at Hct=54, and +31.4% when Hct=56. This can be used to triggeralerts (of escalating severity) based on different levels ofrecalculated RCV variation. The invention provides for treatmentguidance in response to alerts. Treatment for polycythemia includes oneor more of the following: summoning a patient for a consultation with aclinician, to the emergency room, or to receive additional testing suchas blood tests (hemoglobin (Hg), serum erythropoietin (EPO), ferritin,serum iron (FE), or folate), urine and renal function tests, genetictesting for JAK2 mutation, ultrasound, or a stress test; recommendationsfor increased fluid intake; therapeutic phlebotomy; and prescriptionsfor hydroxyurea, ruxolitinib, allopurinol, febuxostat, or low-doseaspirin. The invention also provides for a method of treatingpolycythemia patients using this system, consisting of determining oneor more RCV threshold values, monitoring the patient with the systemdescribed herein, and prescribing treatment in response to alertsreceived.

The invention also provides for a method of treating a patient using thevarious systems described above, wherein (a) the system is used toobtain a first blood volume measurement; (b) one or more thresholds ofblood volume values are set that will be used to trigger alerts; (c) atone or more later times, measuring the patient Hct and using that valueto calculate updated blood volume measurements without repeatedconcentration measurements; (d) receiving alerts from the system whenthe updated blood volume measurements in step (c) pass the thresholdsset in step(b); and (e) treating the patient for the condition.Embodiments for heart failure, syncope, anemia, and polycythemia includespecific treatment options as outlined above.

In another embodiment, positive alerts based on updated blood volumevalues are set in step (b) above, which might trigger the cessation ortapering of treatment, based on a threshold value of a blood volumemeasure in step (b) being reached or maintained for a period of time(such as several days), indicating that the patient's condition hasimproved rather than worsened. For example, a prescribed medicationmight be stopped, or a dosage lowered, or the patient summoned for aconfirmatory examination or testing. In the examples above, positivealerts would be set when higher Hct levels were observed for patientsusing the Heart Failure Decompensation Monitor or the Anemia Monitor;conversely, positive alerts would be set when lower Hct levels wereobserved for patients using the Syncope Monitor or the PolycythemiaMonitor.

FIG. 1 shows a preferred embodiment of the system. A blood volumeanalyzer with guidance (100), such as described in detail in U.S.Provisional Patent Application No. 62/753,174, performs a volumemeasurement (101) of patient XYZ (120). The analyzer produces an initialreport including the patient's volume status and guidance (108), storingthe record of the initial BV measurement (107) for use in calculatingupdated measurements. A Hct monitor (102) provides regular (orcontinuous) measurements of Hct, which are delivered to the analyzer.Various means of fluid intervention (“Blood/Fluids Controller” (103),“Drug Controller” (104), “Ultrafiltration Device” (105),“Erythrocytapheresis Device” (106)), shown with dotted outlines, areoptionally connected to the patient; various interventions can bedelivered to the patient based on the guidance produced by the analyzer.The clinician (121) enters changes to the patient's red cell mass thatoccur after the initial measurement is taken into the analyzer manually(122), when such changes occur as a result of interventions notperformed by components connected to the analyzer. As examples ofautomated treatments, an erythrocytapheresis device may transmit to theanalyzer a measure of the red cell volume that has been removed from thepatient; the Blood/Fluids controller can communicate the volume of redcells delivered. As Hct information (102) and/or manual red cellinformation (122) changes, an updated report (123) is produced usinginformation stored in the Patient XYZ record of Initial BV measurement(107), and shown to clinicians (121).

FIG. 2 shows a preferred embodiment of the system, in which remotemonitoring is used to guide treatment for patients after an initialBlood Volume measurement. On the “Remote Patient Side” (200) variouspatients (211-213) are depicted. Each patient has a Remote Hct Monitorand Transceceiver (201-203), which communicates with a Blood VolumeAnalyzer with Guidance (231), located on the “Clinical Side” (230), e.g.in a hospital or clinic. Each patient has previously had a BVmeasurement performed, and the results of these measurements (232-234)are stored by the analyzer. A clinician (242) manually entersinformation (241) about red-cell altering treatments the variouspatients may have received since their previous BV measurement. Theanalyzer calculates updated volume status and guidance, and providesupdated reports and guidance (251-253) to the clinician. Additionally,each patient is provided with an updated report and guidance (221-223)of their personal status. In a preferred embodiment, the Remote HctMonitor and Transceceiver (201-203) is capable of storing results of theoriginal measurements (232-234) and of calculating and providing updatedreports and guidance (221-223) to the patient without needing tocommunicate further with the analyzer (231).

FIG. 3 shows how the Remote Hct Monitor and Transceiver (201-203)depicted in FIG. 2 can take a variety of forms in various embodiments. Apatient (300) is shown connected to a remote blood volume analyzer withguidance (301) by various means. In a preferred embodiment, anIntegrated Hct Monitor and Transceiver (330) consists of a singleautonomous unit comprising a Hct monitor component, a wireless dataconnection (such as Wifi or cellular capability), and a display; theunit can be worn on or attached to the body (e.g. as a smartwatch orstrap) or be placed in contact with the body (e.g. a finger probe) or incontact with a sample of blood from the body. The monitor componentmeasures the patient Hct; the wireless data connection componentcommunicates with the remote analyzer, and the display presentsinformation to the patient. The functioning of the transceiver in thelarger system is shown in FIG. 2 . In another embodiment, a DeviceTransceiver (320) consists of a local computing device (322) and a Hctmonitor (321). The local computing device (a phone, smartwatch, tablet,laptop, computer, or other device) handles communications with theremote analyzer, using Wifi, cellular, or other data connection. The Hctmonitor is connected to the data device using a wired connection, or awireless connection (Bluetooth, Wifi, or other wireless connection), orvia manual input of values from the monitor into the device. Updatedresults and guidance are conveyed to the patient via the display of thecomputing device or the Hct monitor. In another embodiment, a manualtransceiver system (310) is shown. A Hct monitor (311) measures thePatient's Hct. The patient communicates the Hct value to the clinician(314) via a manual method (312→313) such as a telephone call, textmessage, email, fax, in-person clinical visit, etc. The clinician entersthe updated Hct value into the analyzer (301), which produces an updatedreport (315) which is presented to the clinician. The clinician relaysthe updated report to the patient via the same or other manual means(313→312). In another embodiment of the Manual Transceiver (310), theClinician (314) communicates with a remote Blood Volume Analyzer (301)using a computing device (316).

FIG. 4 shows how a Remote Hct Monitor and Transceiver (401) can becombined with other monitors in various embodiments. A patient (400) isshown connected to a remote blood volume analyzer with guidance (402) bymeans of a Hct Monitor and Transceiver (401). One or more additionalmonitors (410-416) are shown that may be connected to the transceiver,such that the data they provide is used to refine, alter, or supplementthe guidance provided by the analyzer.

In one preferred embodiment, the Remote Hct Monitor and Transceiver iscombined with a Blood Pressure Monitor (410). Many published guidelinesfor management of diverse conditions such as Heart Failure,Hypertension, and Syncope include thresholds for guided treatment usingblood pressure (BP), and these same conditions have guidelines relatedto Blood Volume Measurement. A system or method that incorporatesupdated knowledge of both BP and blood volume can provide improved ormore complete guidance than a system or method that relies on BP alone.

Similarly, in another embodiment, the Remote Hct Monitor and Transceiveris combined with a Pulse Monitor (412). A system or method thatincorporates updated knowledge of both pulse and blood volume canprovide improved or more complete guidance than a system or method thatrelies on pulse alone.

Similarly, in another embodiment, the Remote Hct Monitor and Transceiveris combined with a Photo-plethysmography (PPG) Monitor (416). Thisnon-invasive technology uses visible light signals that are detectedafter being reflected through the skin from near-surface structures of aliving being. PPG sensors are widely used in phones, smarts watches, andother smart wearable devices, and can be applied to various parts of thebody such as fingers, ears, chest, mucous membranes, etc. The analysisof the PPG signal can be used to infer various circulatory measurementsof interest in addition to Hct, such as pulse rate, respiration rate,cardiac stroke rate, peripheral oxygen saturation (SpO2), etc. A systemor method that incorporates updated knowledge of both PPG-derivedmeasurements and blood volume can provide improved or more completeguidance than a system or method that relies on PPG-derived measurementsalone.

Similarly, in another preferred embodiment, the Remote Hct Monitor andTransceiver is combined with an Electro-Magnetic (EM) Monitor (413), forexample one that is capable of revealing fluid in body cavities such asthe lungs. A system or method that incorporates updated knowledge ofboth EM visualization and blood volume can provide improved or morecomplete guidance than a system or method that relies on EMvisualization alone.

In another preferred embodiment, the Remote Hct Monitor and Transceiveris combined with a glucose monitor, and the glucose management is aidedby the reporting of euvolemically corrected glucose values. As disclosedin application publication No. US2018/0217168A1, the euvolemicconcentration of X (eX) that will be observed is changed by the ratio ofV/iV, where V is the volume component that this being considered forpurposes of concentration, and iV is the volume for that component aftera correction to the ideal has been made:

$\begin{matrix}{{eX} = {X*\frac{V}{iV}{where}}} & (33)\end{matrix}$ $\begin{matrix}{\frac{V}{iV} = \left\{ {\begin{matrix}\frac{BV}{iBV} & {{for}{whole}{blood}{concentration}} \\\frac{PV}{{PV} + \left( {{iBV} - {BV}} \right)} & {{for}{plasma}{concentration}}\end{matrix}.} \right.} & (34)\end{matrix}$

The transceiver can display euvolemic whole blood glucose(eGlucose_(wb)), based on the whole blood glucose value Glucose W bgenerally calculated by patient glucose monitors (as opposed to theplasma glucose level Glucose_(plasma) which is generally measures inlabs, and which is most commonly used in guidelines and discussionsabout glucose management).

$\begin{matrix}{{{eGlu}cose_{wb}} = {{Glucose}_{wb}*\frac{BV}{iBV}}} & (35)\end{matrix}$

For glucose management, it is more desirable to display the euvolemicplasma glucose (eGlucose_(plasma)). If Glucose_(plasma) is not measureddirectly, it is generally estimated by a plasma correction factor(plasma_cf), which is usually taken to be in the range 10%-12%:

Glucose_(plasma)=Glucose_(wb)*(1+plasma_(cf))  (36)

Then the euvolemic plasma glucose is:

$\begin{matrix}{{eGlucose_{plasma}} = {{Glucose}_{plasma}*\frac{PV}{{PV} + \left( {{iBV} - {BV}} \right)}}} & (37)\end{matrix}$

corresponding to the plasma glucose level that would likely be observedif the patient's blood volume were corrected to a normal value. Thiseuvolemic plasma glucose has the advantage of being a more accuratemeasure of the total measure of the sugar load of the bloodstream, aswell as potentially providing insight into to the management of patientswho have combined glucose and volume management needs—e.g. heart failurepatients who also have diabetes, a not insignificant fraction.

In another preferred embodiment, a transceiver (401) is connected with ablood gas monitor (414) capable of performing an arterial blood gas(ABG) analysis. A typical analysis might contain measurements of pH,PCO₂, PO₂, SO₂%, HCO₃ ⁻, SBC_(e), total CO₂, O₂ content, etc. Any valuesthat are expressed as concentrations per unit volume can be presented aseuvolemically corrected values. A system or method that incorporatesupdated knowledge of euvolemic ABG and blood volume can provide improvedor more complete guidance than a system or method that relies on ABGalone.

A Comprehensive Blood Monitor (415) is a single device that includesmonitoring or measuring capabilities for a wide variety of analytes,such as electrolytes, metabolites, coagulation, cardiac biomarkers,blood gases, hemoglobin, etc. Any values that are expressed asconcentrations per unit volume can be presented as euvolemicallycorrected values. In a one embodiment, a transceiver (401) is connectedwith a Comprehensive Blood Monitor (415). As comprehensive bloodmonitors often include the capability of measuring Hct, in a preferredembodiment, the Comprehensive Blood Monitor (415) and Remote Hct Monitorand Transceiver (401) are integrated into a single device.

In various other embodiments, a transceiver (401) is connected with oneor more additional monitors, drawn from the set described above(410-415) or other monitors that measure patient characteristics. Forall of the embodiments derived from FIG. 4 discussed above, one skilledin the art would recognize that the connection of the additionalmonitors (410-415) to the transceiver (401) could take various formsranging from integration into a single device, to piecewise connectionsuch as is shown in FIG. 3 .

FIG. 5 . Shows an embodiment of the most generic system. A patient (500)is present whose blood (502) contains a measurable tracer (501). One ormore of the measurements (509) of the concentration of tracer in thepatient's blood are made at an initial time by a concentration counter(503), and the concentration measurements (509) are transmitted to aprocessor (504). Patient descriptive data such as height, weight, andgender (505) is entered via a user interface (506) connected to theprocessor. A Hematocrit monitor (507) measures an initial value for thepatient Hct (508) and transmits this information to the processor (504).The processor uses this information (505, 508, 509) to calculate aninitial blood volume measurement (510) which is stored in memory (511)that is connected to the processor. The processor prepares a report ofthe patient initial volume status (512) and presents it at the displayelement (513) of the user interface (506). At one or more subsequenttimes (depicted in FIG. 5 as dashed rather than solid connecting lines),a subsequent Hct reading (520) is made by the Hct monitor (507), withoutthe need for addition concentration measurements. The processor (504)uses the subsequent Hct reading (520) in conjunction with the initialblood volume measurement information (510) which is stored in memory(511) to calculate a report of the patient updated volume status (522),which is then presented at the display element (513) of the userinterface (506).

All combinations of the various elements described herein are within thescope of the invention unless otherwise indicated herein or otherwiseclearly contradicted by context.

All publications, patents and patent application publications referredto herein are hereby incorporated by reference in their entirety intothe subject application to more fully describe the art to which thesubject invention pertains.

What is claimed is:
 1. A system for automatically analyzing blood of a living patient, comprising a hematocrit (Hct) monitor, one or more processors operatively coupled to a memory and the Hct monitor, a user interface operatively connected to the one or more processors and configured for entry and display of information, where the one or more processors are configured to execute programmed instructions stored in the memory to carry out a method comprising the steps of: a. gathering or receiving data, i. from the user interface, a specified initial deviation from ideal blood volume status, and patient descriptive data; and ii. from the Hct monitor; b. calculating, by the one or more processors, an ideal blood volume (iBV), ideal plasma volume (iPV), and red cell volume (iRCV) for the patient based on patient descriptive data; c. calculating, by the one or more processors, a blood volume (BV), plasma volume (PV), and red cell volume (RCV) for the patient based on data gathered or received in step (a); d. displaying, by the one or more processors, at the user interface, the results of steps (b) and (c); e. storing for later use the results of steps (b) and (c); f. measuring, at one or more later times, an updated value for patient Hematocrit (Hct); g. calculating, by the one or more processors, updated values for BV, PV, and RCV based on the updated Hct, without performing measurements related to the concentration of a tracer within the blood of the patient; and h. displaying, by the one or more processors, at the user interface, the results of step (g).
 2. The system of claim 1, wherein the Hct monitoring function is provided by a Photo-plethysmography (PPG) monitor.
 3. The system of claim 2, where the PPG monitor is configured to detect and send alerts regarding changes in resting heart rate, changes in resting respiration rate, and episodes of atrial fibrillation (Afib).
 4. The system of claim 3, where the system provides guidance specific to the condition of heart failure, where the specified initial deviation from ideal blood volume status in step (a.i) is derived from a combination of clinical judgment based on observation and available tests along with historical reference data for blood volume in similar patients, which indicate that volume overload is common in these patients.
 5. The system of claim 3, where the system provides guidance specific to the condition of syncope, where the specified initial deviation from ideal blood volume status in step (a.i) is derived from a combination of clinical judgment based on observation and available tests along with historical reference data for blood volume in similar patients, which indicate that volume deficit is common in these patients.
 6. The system of claim 5, where the system is configured to detect and send alerts regarding the differences between heart rate when sitting and standing.
 7. The system of claim 3, where the system provides guidance specific to the condition of anemia, where the specified initial deviation from ideal blood volume status in step (a.i) is derived from a combination of clinical judgment based on observation and available tests along with historical reference data for blood volume in similar patients, which indicate that RCV deficit is common in these patients.
 8. A method of analyzing the blood of a living patient, comprising: a. using the system of claim 1 to obtain a first patient blood volume measurement; and b. at one or more later times, measuring the patient Hct and using that value to calculate updated blood volume measurements without repeated concentration measurements.
 9. The method of claim 8, where the system provides guidance specific to the condition of heart failure, where the specified initial deviation from ideal blood volume status in step (a.i) is derived from a combination of clinical judgment based on observation and available tests along with historical reference data for blood volume in similar patients, which indicate that volume overload is common in these patients, and where decreases in measured Hct trigger treatment guidance alerts of increasing severity.
 10. The method of claim 9, wherein the Hct monitoring function is provided by a PPG monitor, and the PPG monitor is configured to detect and send alerts regarding changes in resting heart rate, changes in resting respiration rate, and episodes of atrial fibrillation (Afib).
 11. The method of claim 8, where the system provides guidance specific to the condition of syncope, where the specified initial deviation from ideal blood volume status in step (a) is derived from a combination of clinical judgment based on observation and available tests along with historical reference data for blood volume in similar patients, which indicate that volume deficit is common in these patients, and where increases in measured Hct trigger treatment guidance alerts of increasing severity.
 12. The method of claim 11, wherein the Hct monitoring function is provided by a PPG monitor, and the PPG monitor is configured to detect and send alerts regarding differences between heart rate when sitting and standing, changes in resting heart rate, changes in resting respiration rate, and episodes of atrial fibrillation (Afib).
 13. The method of claim 8, where the system provides guidance specific to the condition of anemia, where the specified initial deviation from ideal blood volume status in step (a) is derived from a combination of clinical judgment based on observation and available tests along with historical reference data for blood volume in similar patients, which indicate that RCV deficit is common in these patients, and where decreases in measured Hct trigger treatment guidance alerts of increasing severity.
 14. The method of claim 13, wherein the Hct monitoring function is provided by a PPG monitor, and the PPG monitor is configured to detect and send alerts regarding tachycardia, changes in resting heart rate, changes in resting respiration rate, and episodes of atrial fibrillation (Afib).
 15. The method of claim 8, where the system provides guidance specific to the condition of polycythemia, where the specified initial deviation from ideal blood volume status in step (a) is derived from a combination of clinical judgment based on observation and available tests along with historical reference data for blood volume in similar patients, which indicate that RCV excess is common in these patients, and where increases in measured Hct trigger treatment guidance alerts of increasing severity.
 16. A method of treating a patient for a condition, comprising: a. using the system of claim 1 to obtain a first patient blood volume measurement, b. setting one or more thresholds of blood volume values that will trigger an alert, c. at one or more later times, measuring the patient Hct and using that value to calculate updated blood volume measurements without repeated concentration measurements; d. receiving alerts from the system when the updated blood volume measurements in step (c) pass the thresholds set in step (b), and e. treating the patient for the condition.
 17. The method of claim 16, where the alerts in step (d) include guidance for specific treatments for the patient's condition.
 18. The method of claim 16, where the condition is heart failure, and the thresholds for the alerts in step (b) are set at TBV values above the initial TBV value, and where the treatments in step (e) include one or more of the following: summoning a patient for a consultation with a clinician, to the emergency room, or to receive additional testing such as blood tests, an X-ray or stress test; prescribing the patient to wear an additional continuous monitor; prescribing or increasing the dose of a diuretic; prescribing or increasing the dose of nitrates; prescribing or increasing the dose of inotropes; prescribing or increasing the dose of vasopressors; and prescribing the use of continuous positive airway pressure (CPAP) mask ventilation.
 19. The method of claim 16, where the condition is syncope, and the thresholds for the alerts in step (b) are set at TBV values below the initial TBV value, and where the treatments in step (e) include one or more of the following: summoning a patient for a consultation with a clinician, to the emergency room, or to receive additional testing such as an electrocardiogram, echocardiogram, stress test, blood tests, autonomic reflex testing, a tilt table test, neurological testing, or a CT scan; prescribing the patient to wear an additional continuous monitor; prescribing or increasing the dose of fludrocortisone acetate; recommending an increase in salt intake; and recommending the use of supportive garments, strengthening exercises, or other behavioral modifications.
 20. The method of claim 16, where the condition is anemia, and the thresholds for the alerts in step (b) are set at RCV values below the initial RCV value, and where the treatments in step (e) include one or more of the following: summoning a patient for a consultation with a clinician, to the emergency room, or to receive additional testing such as blood tests (hemoglobin (Hg), mean cellular volume (MCV), ferritin, serum iron (FE), transferrin, total iron-binding capacity (TIBC), or iron saturation), urine tests, stool tests, ultrasound, or a stress test; prescribing the patient to wear an additional continuous monitor; recommendations for increased dietary iron; and prescriptions for medicinal iron, IV iron, or blood transfusions.
 21. The method of claim 16, where the condition is polycythemia, and the thresholds for the alerts in step (b) are set at RCV values above the initial RCV value, and where the treatments in step (e) include one or more of the following: summoning a patient for a consultation with a clinician, to the emergency room, or to receive additional testing such as blood tests (hemoglobin (Hg), serum erythropoietin (EPO), ferritin, serum iron (FE), and folate), urine and renal function tests, genetic testing for JAK2 mutation, ultrasound, or a stress test; recommendations for increased fluid intake; therapeutic phlebotomy; and prescriptions for hydroxyurea, Ruxolitinib, allopurinol, febuxostat, or low-dose aspirin.
 22. The method of claim 17, where one or more thresholds in step (b) are chosen to indicate that the patient's condition has improved rather than worsened, and where the guidance in step (d) include recommendations for the cessation or tapering of treatment, or for confirmatory examination or testing of the patient. 